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Eunice Kennedy Shriver National Institute of Child Health and Human Development - Program in Cellular Regulation and Metabolism
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Mary Dasso

Mary Dasso's Section on Cell Cycle Regulation uses a variety of metazoan systems, including Xenopus laevis egg extracts, to study mitotic roles of the Ran GTPase, the nuclear pore complex (NPC) and the SUMO family of ubiquitin-like proteins.

These pathways work in an interconnected manner to assure the accurate segregation of chromosomes during mitosis. In the past year, members of the group documented novel roles for both the SUMO pathway and NPC components in the assembly and function of mitotic kinetochores. Particularly the latter aspects of kinetochore function are regulated through Ran.


RanBP1 Governs Spindle Assembly by Defining Mitotic Ran-GTP Production.

RanBP1 Governs Spindle Assembly by Defining Mitotic Ran-GTP Production.

Dev Cell. 2014 Nov 24;31(4):393-404

Authors: Zhang MS, Arnaoutov A, Dasso M

Accurate control of the Ras-related nuclear protein (Ran) GTPase cycle depends on the regulated activity of regulator of chromosome condensation 1 (RCC1), Ran's nucleotide exchange factor. RanBP1 has been characterized as a coactivator of the Ran GTPase-activating protein RanGAP1. RanBP1 can also form a stable complex with Ran and RCC1, although the dynamics and function of this complex remain poorly understood. Here, we show that formation of the heterotrimeric RCC1/Ran/RanBP1 complex in M phase Xenopus egg extracts controls both RCC1's enzymatic activity and partitioning between the chromatin-bound and soluble pools of RCC1. This mechanism is critical for spatial control of Ran-guanosine triphosphate (GTP) gradients that guide mitotic spindle assembly. Moreover, phosphorylation of RanBP1 drives changes in the dynamics of chromatin-bound RCC1 pools at the metaphase-anaphase transition. Our findings reveal an important mitotic role for RanBP1, controlling the spatial distribution and magnitude of mitotic Ran-GTP production and thereby ensuring accurate execution of Ran-dependent mitotic events.

PMID: 25458009 [PubMed - as supplied by publisher]

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